Max dohrn



Patented July 25, 1933 UNITED. STATES. PATENT :oF i

MAX DOHRN, OF BERLIN-CHARLOTTENBURG, AN D PAUL DIEDEICI-I,

OF FINKENKRUG NEAR SPANDAUGERMANY, ASSIGNORS T0 SCHERING-KAHLBAUM A. 6%., OF BERLIN,

GERMANY CHELID-AMIO Aci'n coral-0on3 No Drawing. Application filed June 17, 1931, Serial No. 545,074, and in Germany December 18,1930.

Our invention refers to new chemical compounds of the chelidamic acid series, which have proven to be particularly usefulfor medical diagnosis and to the method of producing same. Y

The sodium salt of di-iodo chelidamic acid has hitherto been used in the practice of pyelographic diagnosis, i. e. in the production of X-ray pictures with intravenous injection of this salt. It has however been found that this compound is apt to produce an increase of the blood pressure and an excitation of the respiratory center. These effects are obviously due to the tautomeric character of the hy droxyl group in 4-position illustrated as follows:

- pressure will not occur if the alkali metal salts of di-iodochelidamic acid are replaced by salts of the N-methyl di-iodo chelidamic acid having the formula:

I I HOOCL OOOH The N-methyl di-iodo chelidamic acid is a colorless, well crystallizing acid, which is little soluble in water and melts at 174 0., carbon dioxide being split off. lVith'a caustic V alkaline medium with a methylating agent, such as methyl halide or methyl sulfate.

- Example 1 1 43.5 grs. di-iodo chelidainic acid are dissolved 1n an excess of caustic potash and38 grs. methyl sulfate are slowly added to the heated "solution. under vigorous I stirring. After the methyl-sulfate has been added, stirring is continued during one hour until the.

the precipitate is takenup with water. The reddish brown ironsalt of di-iodo chelidamic acid is precipitated by addingferric chloride and the salt is separated by suction. From the filtrate the ferric chloride in excess is pre cipitated in the form ofhydroxide by the addition of an alkali and after filtration the pure N-methyl di-iodo chelidamic acid is-separated'out by adding hydrochloric acid.

The N-methyl di-icdo chelidamic acid is- =.i

decomposed at 174 (3., carbon dioxide being split off. It readily dissolves in water, less readily in alcohol and ether.

From the ferric salt of the di-iodo chelidamic acid the free acid can readily be re-;

covered by over-acidifying with hydro chloric acid.

13.5 grs. di-iodo chelidamic acid are dis solved in 300 ccms. normal caustic'potash solution and boiled during 5 hours under. the reflux condenser with 13 grs. methyl iodide. On acidification the N-methyl di-iodo chelidamic acid is precipitated, which can be purified as explained with reference to Example 1.

10 grs. of' the silver salt of di-iodo cheli damic acid dimethyl ester are heated during one hour to the boilingpoin't with 3 grs.

propyl iodide and 100 coins. Xylene. The

solution is filtered, while still hot and after V wherein X is hydrogen or an alkali metal,

cooling the N-propyl di-iodo chelidamic acid dimethyl ester is separated out by adding petroleum ether. By saponification of the N-propyl di-iodo chelidamic acid dimethyl ester, melting at 89 C., there is produced N- propyl di-iodo chelidamic acid, which crystallizes in the form of cubes and melts at 156 (1, carbon dioxide being split off.

Ewczm-ple .4.-N- Znrt Z (ii-dado ohclz damio acid 10 grs. of the silver salt of the di-iodo chelidamic acid dimethyl ester are boiled during one hour with 3.5 grs. butyl iodide and 100 ccms. Xylene. The reaction mixture is treated further as described with reference to Example 3. r r

The N-butyl di-odo chelidamic acid dimethyl ester melts at 82 C.

p The- N -b-utyl di-iodo 'chelidamic acid crystallizes in the form of needles andmelts at 145 0., carbon dioxide being split off.

Various changes may be made in the details disclosed in-the foregoing specification Without departing from the invention or sacrificing the advantages thereof.

' WVe claim: 1. Compounds having the formula It I ji xoocl -OOOX v N 7 the compound, if X is hydrogen, being a well crystallizin colorless water-soluble acid melting at 1 74 C, under formation of carbon dioxide, forming with an alkali a readily water-soluble salt, but not showing the reaction with ferric chloride peculiar to the pyridones. I o

2. The alkali-metal salts of N-methyl diiodo chelidamic acid NHOOC L J-OOONa chelidamic acid said salt, when treated with hydrochloric acid in excess, separating out the free N-ethyl di-iodo chelidamic acid as a well crystallizing colorless acid melting at 174 C. under separation of carbon dioxide.

- MAX DOHRN.

PAUL DIEDRICH. 

